Molecular mechanism of elastic fiber assembly.

弹性纤维在弹性组织如动脉、肺和皮肤中丰富，并为这些组织提供弹性。与年龄相关的弹性纤维变性或断裂导致动脉硬化、肺气肿和皮肤松弛。因此，深入研究弹力纤维发生的分子机制，对将来的弹力纤维再生治疗具有重要意义。我们先前报道了一种分泌蛋白Fibulin-5是弹性纤维组装所必需的。在这项研究中，我们研究了Fibulin-4，同一个蛋白质家族的成员，在弹性发生中的作用。平滑肌特异性敲除小鼠Fbln 4基因导致腰椎和动脉瘤弹性层退化。我们还发现，纤蛋白-4直接与赖氨酰氧化酶和原弹性蛋白相互作用，从而将酶拴在其底物上。

Elastic fiber is abundant in elastic tissues such as arteries, lungs and skin, and provides elasticity to these tissues. Aging-associated elastic fiber degeneration or fragmentation causes arteriosclerosis, emphysema and loose skin. It is important to uncover the molecular mechanism of elastogenesis for the future elastic fiber regeneration therapy. We previously reported that a secreted protein Fibulin-5 is essential for elastic fiber assembly. In this study, we studied the role for Fibulin-4, a member of the same protein family, in elastogenesis. Smooth muscle-specific knockout of the mouse Fbln4 gene resulted in degenerated elastic laminae in aortae and aneurysm. We also found that Fibulin-4 directly interacts with lysyl oxidase and tropoelastin, thereby tethering the enzyme to its substrate.